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1.
Axonal regeneration after injury to the CNS is hampered by myelin‐derived inhibitors, such as Nogo‐A. Natural products, such as green tea, which are neuroprotective and safe for long‐term therapy, would complement ongoing various pharmacological approaches. In this study, using nerve growth factor‐differentiated neuronal‐like Neuroscreen‐1 cells, we show that extremely low concentrations of unfractionated green tea polyphenol mixture (GTPP) and its active ingredient, epigallocatechin‐3‐gallate (EGCG), prevent both the neurite outgrowth‐inhibiting activity and growth cone‐collapsing activity of Nogo‐66 (C‐terminal domain of Nogo‐A). Furthermore, a synergistic interaction was observed among GTPP constituents. This preventive effect was dependent on 67‐kDa laminin receptor (67LR) to which EGCG binds with high affinity. The antioxidants N‐acetylcysteine and cell‐permeable catalase abolished this preventive effect of GTPP and EGCG, suggesting the involvement of sublethal levels of H2O2 in this process. Accordingly, exogenous sublethal concentrations of H2O2, added as a bolus dose (5 μM) or more effectively through a steady‐state generation (1–2 μM), mimicked GTPP in counteracting the action of Nogo‐66. Exogenous H2O2 mediated this action by bypassing the requirement of 67LR. Taken together, these results show for the first time that GTPP and EGCG, acting through 67LR and elevating intracellular sublethal levels of H2O2, inhibit the antineuritogenic action of Nogo‐A.

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Crop improvement is a long-term, expensive institutional endeavor. Genomic selection (GS), which uses single nucleotide polymorphism (SNP) information to estimate genomic breeding values, has proven efficient to increasing genetic gain by accelerating the breeding process in animal breeding programs. As for crop improvement, with few exceptions, GS applicability remains in the evaluation of algorithm performance. In this study, we examined factors related to GS applicability in line development stage for grain yield using a hard red winter wheat (Triticum aestivum L.) doubled-haploid population. The performance of GS was evaluated in two consecutive years to predict grain yield. In general, the semi-parametric reproducing kernel Hilbert space prediction algorithm outperformed parametric genomic best linear unbiased prediction. For both parametric and semi-parametric algorithms, an upward bias in predictability was apparent in within-year cross-validation, suggesting the prerequisite of cross-year validation for a more reliable prediction. Adjusting the training population’s phenotype for genotype by environment effect had a positive impact on GS model’s predictive ability. Possibly due to marker redundancy, a selected subset of SNPs at an absolute pairwise correlation coefficient threshold value of 0.4 produced comparable results and reduced the computational burden of considering the full SNP set. Finally, in the context of an ongoing breeding and selection effort, the present study has provided a measure of confidence based on the deviation of line selection from GS results, supporting the implementation of GS in wheat variety development.  相似文献   
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Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10?5 M) in the presence of selective M2 antagonist methoctramine (10?7 M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10?8 M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+ currents I to, I Kur, and I Kir. In the absence of M2 blocker methoctramine, pilocarpine (10?5 M) produced stronger attenuation of I CaL and induced an increase in I Kir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10?6 M) and therefore was identified as I KACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of I CaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of I KACh.  相似文献   
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Exposure of endothelial cells (ECs) to agents such as oxidized glycerophospholipids (oxGPs) and cytokines, known to accumulate in atherosclerotic lesions, perturbs the expression of hundreds of genes in ECs involved in inflammatory and other biological processes. We hypothesized that microRNAs (miRNAs) are involved in regulating the inflammatory response in human aortic endothelial cells (HAECs) in response to oxGPs and interleukin 1β (IL-1β). Using next-generation sequencing and RT-quantitative PCR, we characterized the profile of expressed miRNAs in HAECs pre- and postexposure to oxGPs. Using this data, we identified miR-21-3p and miR-27a-5p to be induced 3- to 4-fold in response to oxGP and IL-1β treatment compared with control treatment. Transient overexpression of miR-21-3p and miR-27a-5p resulted in the downregulation of 1,253 genes with 922 genes overlapping between the two miRNAs. Gene Ontology functional enrichment analysis predicted that the two miRNAs were involved in the regulation of nuclear factor κB (NF-κB) signaling. Overexpression of these two miRNAs leads to changes in p65 nuclear translocation. Using 3′ untranslated region luciferase assay, we identified 20 genes within the NF-κB signaling cascade as putative targets of miRs-21-3p and -27a-5p, implicating these two miRNAs as modulators of NF-κB signaling in ECs.  相似文献   
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Herbivory is a fundamental process that controls primary producer abundance and regulates energy and nutrient flows to higher trophic levels. Despite the recent proliferation of small‐scale studies on herbivore effects on aquatic plants, there remains limited understanding of the factors that control consumer regulation of vascular plants in aquatic ecosystems. Our current knowledge of the regulation of primary producers has hindered efforts to understand the structure and functioning of aquatic ecosystems, and to manage such ecosystems effectively. We conducted a global meta‐analysis of the outcomes of plant–herbivore interactions using a data set comprised of 326 values from 163 studies, in order to test two mechanistic hypotheses: first, that greater negative changes in plant abundance would be associated with higher herbivore biomass densities; second, that the magnitude of changes in plant abundance would vary with herbivore taxonomic identity. We found evidence that plant abundance declined with increased herbivore density, with plants eliminated at high densities. Significant between‐taxa differences in impact were detected, with insects associated with smaller reductions in plant abundance than all other taxa. Similarly, birds caused smaller reductions in plant abundance than echinoderms, fish, or molluscs. Furthermore, larger reductions in plant abundance were detected for fish relative to crustaceans. We found a positive relationship between herbivore species richness and change in plant abundance, with the strongest reductions in plant abundance reported for low herbivore species richness, suggesting that greater herbivore diversity may protect against large reductions in plant abundance. Finally, we found that herbivore–plant nativeness was a key factor affecting the magnitude of herbivore impacts on plant abundance across a wide range of species assemblages. Assemblages comprised of invasive herbivores and native plant assemblages were associated with greater reductions in plant abundance compared with invasive herbivores and invasive plants, native herbivores and invasive plants, native herbivores and mixed‐nativeness plants, and native herbivores and native plants. By contrast, assemblages comprised of native herbivores and invasive plants were associated with lower reductions in plant abundance compared with both mixed‐nativeness herbivores and native plants, and native herbivores and native plants. However, the effects of herbivore–plant nativeness on changes in plant abundance were reduced at high herbivore densities. Our mean reductions in aquatic plant abundance are greater than those reported in the literature for terrestrial plants, but lower than aquatic algae. Our findings highlight the need for a substantial shift in how biologists incorporate plant–herbivore interactions into theories of aquatic ecosystem structure and functioning. Currently, the failure to incorporate top‐down effects continues to hinder our capacity to understand and manage the ecological dynamics of habitats that contain aquatic plants.  相似文献   
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  • Studies on plant electrophysiology are mostly focused on specific traits of single cells. Inspired by the complexity of the signalling network in plants, and by analogy with neurons in human brains, we sought evidence of high complexity in the electrical dynamics of plant signalling and a likely relationship with environmental cues.
  • An EEG‐like standard protocol was adopted for high‐resolution measurements of the electrical signal in Glycine max seedlings. The signals were continuously recorded in the same plants before and after osmotic stimuli with a ?2 MPa mannitol solution. Non‐linear time series analyses methods were used as follows: auto‐correlation and cross‐correlation function, power spectra density function, and complexity of the time series estimated as Approximate Entropy (ApEn).
  • Using Approximate Entropy analysis we found that the level of temporal complexity of the electrical signals was affected by the environmental conditions, decreasing when the plant was subjected to a low osmotic potential. Electrical spikes observed only after stimuli followed a power law distribution, which is indicative of scale invariance.
  • Our results suggest that changes in complexity of the electrical signals could be associated with water stress conditions in plants. We hypothesised that the power law distribution of the spikes could be explained by a self‐organised critical state (SOC) after osmotic stress.
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Potassium inward rectifier KIR2.1 channels contribute to the stable resting membrane potential in a variety of muscle and neuronal cell-types. Mutations in the KIR2.1 gene KCNJ2 have been associated with human disease, such as cardiac arrhythmias and periodic paralysis. Crystal structure and homology modelling of KIR2.1 channels combined with functional current measurements provided valuable insights in mechanisms underlying channel function. KIR2.1 channels have been cloned and analyzed from all main vertebrate phyla, except reptilians. To address this lacuna, we set out to clone reptilian KIR2.1 channels. Using a degenerated primer set we cloned the KCNJ2 coding regions from muscle tissue of turtle, snake, bear, quail and bream, and compared their deduced amino acid sequences with those of KIR2.1 sequences from 26 different animal species obtained from Genbank. Furthermore, expression constructs were prepared for functional electrophysiological studies of ectopically expressed KIR2.1 ion channels. In general, KCNJ2 gene evolution followed normal phylogenetic patterns, however turtle KIR2.1 ion channel sequence is more homologues to avians than to snake. Alignment of all 31 KIR2.1 sequences showed that all disease causing KIR2.1 mutations, except V93I, V123G and N318S, are fully conserved. Homology models were built to provide structural insights into species specific amino acid substitutions. Snake KIR2.1 channels became expressed at the plasmamembrane and produced typical barium sensitive (IC50 ∼6 μM) inward rectifier currents.  相似文献   
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